A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.
de Vries PS., Chasman DI., Sabater-Lleal M., Chen M-H., Huffman JE., Steri M., Tang W., Teumer A., Marioni RE., Grossmann V., Hottenga JJ., Trompet S., Müller-Nurasyid M., Zhao JH., Brody JA., Kleber ME., Guo X., Wang JJ., Auer PL., Attia JR., Yanek LR., Ahluwalia TS., Lahti J., Venturini C., Tanaka T., Bielak LF., Joshi PK., Rocanin-Arjo A., Kolcic I., Navarro P., Rose LM., Oldmeadow C., Riess H., Mazur J., Basu S., Goel A., Yang Q., Ghanbari M., Willemsen G., Rumley A., Fiorillo E., de Craen AJM., Grotevendt A., Scott R., Taylor KD., Delgado GE., Yao J., Kifley A., Kooperberg C., Qayyum R., Lopez LM., Berentzen TL., Räikkönen K., Mangino M., Bandinelli S., Peyser PA., Wild S., Trégouët D-A., Wright AF., Marten J., Zemunik T., Morrison AC., Sennblad B., Tofler G., de Maat MPM., de Geus EJC., Lowe GD., Zoledziewska M., Sattar N., Binder H., Völker U., Waldenberger M., Khaw K-T., Mcknight B., Huang J., Jenny NS., Holliday EG., Qi L., Mcevoy MG., Becker DM., Starr JM., Sarin A-P., Hysi PG., Hernandez DG., Jhun MA., Campbell H., Hamsten A., Rivadeneira F., Mcardle WL., Slagboom PE., Zeller T., Koenig W., Psaty BM., Haritunians T., Liu J., Palotie A., Uitterlinden AG., Stott DJ., Hofman A., Franco OH., Polasek O., Rudan I., Morange P-E., Wilson JF., Kardia SLR., Ferrucci L., Spector TD., Eriksson JG., Hansen T., Deary IJ., Becker LC., Scott RJ., Mitchell P., März W., Wareham NJ., Peters A., Greinacher A., Wild PS., Jukema JW., Boomsma DI., Hayward C., Cucca F., Tracy R., Watkins H., Reiner AP., Folsom AR., Ridker PM., O'Donnell CJ., Smith NL., Strachan DP., Dehghan A.
Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.